Association between optical coherence tomography–quantified retinal features and cardiovascular risk in cardiovascular–kidney–metabolic syndrome stages 0–3: An analysis of a prospective UK biobank cohort

Abstract

Background Cardiovascular–kidney–metabolic (CKM) syndrome is strongly associated with cardiovascular disease (CVD) and mortality. Stages 0–3 represent a key preclinical window for early intervention. Retinal optical coherence tomography (OCT) enables non-invasive evaluation of systemic microcirculation, but its prognostic value for CVD in CKM 0–3 remains undetermined. Methods We conducted a prospective study of 40,516 UK Biobank participants with CKM syndrome stages 0–3 who had retinal OCT. Cox regression, trend tests, and predictive metrics (NRI, IDI, AUC) were used to evaluate associations and incremental prognostic value of retinal structural markers. Results Baseline thinner retinal nerve fiber layer (RNFL) and macular thickness were independently associated with higher risks of incident CVD, coronary heart disease, all-cause mortality, and cardiovascular mortality over a subsequent median 14.6-year follow-up (all P < 0.001). Significant linear dose–response relationships were observed. Adding these markers to traditional risk models improved risk classification and discrimination (all P < 0.001). Conclusion Thinner RNFL and macular thickness are independent predictors of adverse cardiovascular outcomes in CKM 0–3. Integrating these OCT-derived biomarkers improves risk stratification, supporting a non-invasive approach for early cardiovascular risk assessment in this high-risk population.